Mettl3-Catalyzed m6A Regulates Histone Modifier and Modification Expression in Self-Renewing Somatic Tissue

    September 2023 in “ Science Advances ”
    Alexandra M. Maldonado López, Eun Kyung Ko, Sijia Huang, Gina Pacella, Nina Kuprasertkul, C. D'souza, Raúl A. Reyes Hueros, Hui Shen, Julian Stoute, Heidi Elashal, Morgan Sinkfield, Amy Anderson, Stephen M. Prouty, Huabing Li, John T. Seykora, Kathy Fange Liu, Brian C. Capell
    TLDR Mettl3 is essential for normal tissue development and self-renewal by regulating gene expression.
    The study explores the role of Mettl3-catalyzed N6-methyladenosine (m6A) in regulating gene expression and chromatin modifiers in self-renewing somatic tissues, focusing on epithelial development. By deleting Mettl3 in mice epidermal progenitors, researchers observed significant developmental issues, such as impaired hair growth and malformed hair follicles, highlighting Mettl3's critical role in epithelial development. The absence of Mettl3 led to transcriptional dysregulation, with nearly 4000 genes showing differential expression, affecting pathways related to keratinization, differentiation, and cell adhesion. The study underscores the importance of Mettl3 and m6A in maintaining epithelial homeostasis and suggests potential therapeutic targets for epithelial diseases and cancers by modulating Mettl3 activity.
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